Step 1: Dissolve 3-methylisothiazol-5-ylamine hydrochloride in ethyl acetate and wash with 10% sodium carbonate solution to convert it into a free base. Dry and evaporate the organic phase to obtain the free 3-methylisothiazol-5-ylamine base. Step 2: Dissolve 3-methylisothiazol-5-ylamine (6.0 g, 52.55 mmol) in orthophosphoric acid (20 mL) and cool to 0 °C. Add nitric acid (10 mL) dropwise, followed by sodium nitrite (4.17 g, 60.44 mmol) dropwise, maintaining the temperature between 0 and 5 °C. Stir the reaction mixture at 10 °C for 30 minutes, then add it dropwise to a mixture of copper bromide (I) (9.5 g, 63.06 mmol) in 48% HBr aqueous solution (100 mL), and stir the resulting mixture at room temperature for 1 hour. The pH was adjusted to 6-7 using 4N sodium hydroxide, water (500 mL) was added, and then steam distillation was performed using water (2 × 500 mL) on a rotary evaporator. The aqueous layer was extracted with diethyl ether (x2), and the organic phase was dried with sodium sulfate, filtered, and the solvent was evaporated to give the title compound 5-bromo-3-methylisothiazol (7.0 g).
